Reactive oxygen species could aid in cancer treatment
Reactive oxygen species (ROS) are molecules belonging to two groups: free radicals having one or more unpaired electron(s) such as superoxide (O2–), hydroxyl radical (OH●), and nitric oxide (NO●); and non-radical ROS with no unpaired electrons such as hydrogen peroxide (H2O2) or singlet oxygen (1O2). ROS are naturally produced by the mitochondrial electron transport chain during aerobic respiration, oxidoreductase enzymes and metal ion-catalyzed oxidation. They are essential for several biological functions as they react with and modify the structure of genes and proteins to modulate their functions. They also act as second messenger molecules in a variety of signaling cascades including cell proliferation and differentiation.
Elevated levels of ROS have been found in most cancers, supposedly due to an increase in metabolic activity, mitochondrial dysfunction, and relative lack of blood supply compared to normal cells. It is well documented that ROS act in multiple signaling cascades involved in cancer initiation, development, progression, invasion and metastasis. Therefore, they are deemed to be oncogenic. The use of antioxidants such as polyphenols has been considered a reasonable therapeutic approach to treat ROS-induced cancers. Interestingly, there is an increasing number of evidence suggesting a totally opposite role for ROS: it seems that both extrinsic and intrinsic forms of apoptosis can be triggered by relatively high levels of ROS. As with all therapies, efficiency and selectivity of the treatment are essential and the question remains on how tumor cells can be efficiently and selectively killed by ROS. The current hypothesis is that a moderate increase of ROS may promote cell proliferation and survival whereas an excessive increase of ROS may trigger cell death. Because healthy cells maintain redox homeostasis and have lower basal levels of ROS than cancer cells, they can better tolerate a certain level of exogenous stress than cancer cells. The latter reach the critical threshold earlier and ultimately undergo cell death by apoptosis while healthy cells may survive.
Recently, Dr. Tang and colleagues from the University of Kansas Medical Center defined a natural compound called Alternol as a promising novel anticancer drug for advanced prostate cancer. Alternol is a compound purified from the fermentation products of Alternaria alternate var. monosporus. The authors demonstrated that Alternol induces prostate cancer cell-specific apoptosis through severe intracellular accumulation of ROS. Alternol-induced apoptosis of prostate cancer cells was shown to be dependent on the expression of the pro-apoptotic protein Bax. Indeed, prostate cancer cells negative for the expression of Bax were insensitive to Alternol-induced ROS accumulation. Overall, these data suggest that Alternol has a great potential as an anticancer agent.
